The isolation of specific cell populations from complex mixtures such as whole blood has significant utility in both clinical practice and basic medical research. A variety of approaches can be used to separate cells from a heterogeneous sample. For example, some techniques can use functionalized materials to capture cells by binding cell surface markers that are particular to the target cell population. The functionalized materials can include surface-bound capture moieties such as antibodies or other specific binding molecules, such as aptamers or selectins.
Viable tumor-derived epithelial cells (e.g., circulating tumor cells or CTCs) have been identified in peripheral blood from cancer patients and are likely the origin of intractable metastatic disease. The isolation of CTCs represents a potential alternative to invasive biopsies as a source of tumor tissue for the detection, characterization, and monitoring of non-hematologic cancers. The ability to identify, isolate, propagate, and molecularly characterize CTC subpopulations could further the discovery of cancer stem cell biomarkers and expand the understanding of the biology of metastasis. Current strategies for isolating CTCs are limited to complex analytic approaches that generate very low yield and purity. CTCs are considered to be rare, making up as few as about 1 CTC per 109 hematologic cells in the blood of patients with metastatic cancer. Thus, the isolation of CTCs from blood samples presents a tremendous technical challenge.
Microfluidic lab-on-a-chip devices can be used for cell sorting and rare cell detection. Such devices have been used for microfluidic flow cytometry, continuous size-based separation, and chromatographic separation. For example, a microfluidic affinity-based chip that is configured to isolate CTCs from the whole blood of cancer patients is described, e.g., in Nagrath et al., “Isolation of rare circulating tumor cells in cancer patients by microchip technology,” Nature 450: 1235-1239 (2007). CTCs may disseminate from the tumor and are observed to be present in numbers that tend to correlate with patients' clinical courses. CTCs may also be involved in metastasis. Accordingly, such microfluidic chip technology can be used in diagnostic and prognostic devices for oncological applications.
However, the capture of CTCs from a blood sample on the surface of a microfluidic channel using surface-bound antibodies, such as an anti-Epithelial Cell Adhesion Molecule (EpCAM) antibody can be difficult due to both the rarity of the CTCs in the sample and/or reduced levels of CTC expression of the antigen corresponding to the surface-bound antibody. Accordingly, there remains a need for methods and devices for improving the detection levels of CTCs in biological samples.